The present research proposal evolved from a clinical study in which we found that LHRH was luteolytic when administered during the luteal phase of the cycle. In the same study, it was found that pharmacologic doses of gonadotropin did not cause apparent down-regulation of luteal LH receptors as it did the rat. More recently, we showed that LHRH and LHRH analogs showed acute and direct antigonadotropic activity in rat luteal cells. The objective of the present proposal is first to determine if LHRH and LHRH analogs show direct antigonadotropic activity in human ovarian cells in vitro and, if so, evaluate the cellular basis of this activity; second, to assess if LHRH may play a physiological (and/or pathological) role as a direct modulator of gonadotropin action in the ovary; and third, examine whether other antigonadotropic proteins (peptides) serving such functions may be present in ovarian and uterine tissues and fluids. This research will be based on cell dispersion and short- and long-term culture techniques, radioimmunoassay of gonadal steroids and LHRH, receptor binding studies for LHRH and LH, and protein-peptide extraction and assay techniques. This information may lead to an understanding of the mechanism of the luteolytic action of LHRH in the human female and possibly identify other antigonadotropins of ovarian origin of which LHRH is a pharmacologic agonist.